title: Progression of vertebral fractures despite long-term biochemical control of acromegaly: a prospective follow-up study.
abstract: BACKGROUND
  In active acromegaly, pathologically elevated GH and IGF-1 levels are associated with increased bone turnover and a high bone mass, the latter being sustained after normalization of GH values. In a cross-sectional study design, we have previously reported a high prevalence of vertebral fractures (VFs) of about 60% in patients with controlled acromegaly, despite normal mean bone mineral density (BMD) values. Whether these fractures occur during the active acromegaly phase or after remission is achieved is not known.
  
  
  OBJECTIVE
  Our objective was to study the natural progression of VFs and contributing risk factors in patients with controlled acromegaly over a 2.5-year follow-up period.
  
  
  METHODS
  Forty-nine patients (mean age 61.3 ± 11.1 years, 37% female) with controlled acromegaly for ≥ 2 years after surgery, irradiation, and/or medical therapy and not using bisphosphonates were included in the study. Conventional spine radiographs including vertebrae Th4-L4 were assessed for VFs according to the Genant method. VF progression was defined as development of new/incident fractures and/or a minimum 1-point increase in the Genant scoring of preexisting VFs. BMD was assessed by dual-energy x-ray absorptiometry (Hologic 4500).
  
  
  RESULTS
  Prevalence of baseline VFs was 63%, being highest in men, and fractures were unrelated to baseline BMD. VF progression was documented in 20% of patients, especially in men and in case of ≥ 2 VFs at baseline. VF progression was not related to BMD values or BMD changes over time.
  
  
  CONCLUSIONS
  Findings from this longitudinal study show that VFs progress in the long term in 20% of patients with biochemically controlled acromegaly in the absence of osteoporosis or osteopenia. These data suggest that an abnormal bone quality persists in these patients after remission, possibly related to pretreatment long-term exposure to high circulating levels of GH.
authors.affiliation: Department of Endocrinology and Metabolic Diseases C7-Q, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands. K.M.J.A.Claessen@lumc.nl.
authors.forename: K M J A
authors.initials: KM
authors.lastname: Claessen
authors.forename: H M
authors.initials: HM
authors.lastname: Kroon
authors.forename: A M
authors.initials: AM
authors.lastname: Pereira
authors.forename: N M
authors.initials: NM
authors.lastname: Appelman-Dijkstra
authors.forename: M J
authors.initials: MJ
authors.lastname: Verstegen
authors.forename: M
authors.initials: M
authors.lastname: Kloppenburg
authors.forename: N A T
authors.initials: NA
authors.lastname: Hamdy
authors.forename: N R
authors.initials: NR
authors.lastname: Biermasz
mesh_terms: D000172:Acromegaly / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D000368:Aged; D015519:Bone Density; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000503:physiopathology / Q000628:therapy*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D015995:Prevalence; D011446:Prospective Studies; D011859:Radiography; D012008:Recurrence; D012074:Remission Induction; D012307:Risk Factors; D012737:Sex Factors; D016103:Spinal Fractures / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000209:etiology* / Q000503:physiopathology*; D013131:Spine / Q000000981:diagnostic imaging